Rapid improvement in antineoplastic therapy is increasing not only cancer survivorship but also the incidence of end-stage heart failure among breast and childhood cancer survivors. Anthracyclines and newer targeted therapies, including trastuzumab and tyrosine kinase inhibitors, are important agents implemented in clinical practice that carry cardiotoxic risk. While acute heart failure is often self-limited and reversible, delayed-onset heart failure significantly reduces survival. Extremes of age, renal dysfunction, pre-existing coronary artery disease, HER2 positivity, and multi-drug therapy are predictors of irreversible heart failure after chemotherapy. Left ventricular assist device (LVAD) implantation and cardiac transplantation can be performed safely in patients with end-stage heart failure (HF) from chemotherapy. However, co-existing right ventricular dysfunction, hepatic congestion, and increased risk of bleeding make LVAD therapy challenging and dependent on careful patient selection. Cardiac transplantation in patients with chemotherapy-induced heart failure can be performed with good 10-year survival, but requires 5 years of cancer freedom and post-transplant infections remain a problem. Improvements in LVAD therapy and the expanding role of the total artificial heart and other durable biventricular support devices will likely provide more reliable surgical options for the management of end-stage HF after chemotherapy.